Evaluation of the effect of biperiden (cholinergic muscarinic receptor antagonist) on ethanol self-administration in rats

Evidence from the literature suggests that alcohol use disorder (AUD) is closely associated with alterations in neuronal plasticity and the memory system, related to modifications in muscarinic receptors. The present study aimed to investigate the effects of systemic injection of biperiden, a muscarinic cholinergic antagonist, in experimental protocols of progressive ratio, 24-hour binge alcohol consumption, and reinstatement of context-induced ethanol self-administration. The results demonstrated that biperiden at doses of 5 and 10 mg/kg (i.p.) effectively reduced the animals' motivation for alcohol consumption, as evidenced by decreased responses on the active lever and a reduction in the last ratio achieved in the progressive ratio protocol. Furthermore, these same doses significantly reduced ethanol consumption in the 24-hour binge protocol. Treatment with biperiden at doses of 1, 5, and 10 mg/kg also attenuated alcohol-seeking behavior after re-exposure to the context associated with ethanol self-administration. These findings suggest that biperiden may have therapeutic potential in the treatment of alcohol use disorder, indicating that modulation of the cholinergic system could be a promising avenue for further investigation.